Risk factors for neuroendocrine tumours

A risk factor is something that increases the risk of developing cancer. It could be a behaviour, substance or condition. Most cancers are the result of many risk factors. But sometimes neuroendocrine tumours (NETs) develop in people who don’t have any of the risk factors described below.

NETs can develop at any age, but most cases occur in people 60 years of age and older. The number of new cases of NETs diagnosed each year has been rising for about the last 20 years. Researchers think this rise in the incidence is because better diagnostic tests, especially imaging tests, are helping to find these tumours.

Risk factors are generally listed in order from most to least important. But in most cases, it is impossible to rank them with absolute certainty.

Known risk factors

There is convincing evidence that the following factors increase your risk for NETs.

Hereditary conditions

A hereditary condition is a disorder that is passed from a parent to their child through genes. It is caused by a change, or mutation, in one or more genes. The following are rare hereditary conditions that can increase the risk of developing certain types of NETs.

Multiple endocrine neoplasia

Multiple endocrine neoplasia (MEN) is caused by an inherited mutation of the MEN1 gene, RET gene or CDKN1B gene. People with MEN can develop many NETs and endocrine gland tumours. These tumours can be non-cancerous (benign) or cancerous (malignant).

There are 4 types of MEN (MEN1, MEN2A, MEN2B and MEN4). The types of tumours that develop depends on the type of MEN.

MEN1 most often causes NETs to develop in the parathyroid glands, pancreas and pituitary gland. Sometimes people with MEN1 develop gastrointestinal NETs (GI NETs) or lung NETs.

Most people with MEN2A or MEN2B will develop medullary carcinoma, which is a type of thyroid cancer. MEN2A and MEN2B can also cause other types of tumours, including pheochromocytomas and parathyroid adenomas.

The most common types of NETs to develop in people with MEN4 are parathyroid adenomas and pituitary adenomas.

Von Hippel-Lindau syndrome

Von Hippel-Lindau syndrome is caused by a mutation of VHL gene. People with von Hippel-Lindau syndrome can develop tumours and cysts in different parts of the body. These tumours include NETs, such as pheochromocytomas and pancreatic NETs.

Neurofibromatosis type 1

Neurofibromatosistype 1 is caused by a mutation of the NF1 gene. The mutation can be inherited or it can happen by chance (called a sporadic mutation). People with neurofibromatosis type 1 often develop many neurofibromas, which are non-cancerous tumours of nerves and skin. They also have a higher risk of developing gastrointestinal NETs, gastrointestinal stromal tumours (GISTs), pancreatic NETs and pheochromocytomas.

Tuberous sclerosis

Tuberous sclerosis can cause non-cancerous tumours to form in many organs of the body, including the eyes, skin, brain, lungs, heart and kidneys. People with tuberous sclerosis also have a higher risk of developing NETs.

Family history of cancer

Many studies show that a family history of any type of cancer increases your risk of developing a NET, especially if the person with cancer is your first-degree relative (a parent, sibling or child). It is unclear if the higher risk is due to genetic factors or similar lifestyle factors of family members.

A few studies have linked a family history of a specific type of cancer with developing a NET. For example, a family history of lung cancer can increase the risk of developing lung NETs. Also, a family history of colorectal or breast cancer is linked with developing NETs in the small intestine. People with a family history of cancer can also develop NETs in the pancreas or stomach.

Possible risk factors

The following factors have been linked with NETs, but there is not enough evidence to show they are known risk factors. More research is needed to clarify the role of these factors for NETs.

Smoking

Some studies show that smoking tobacco increases the risk of developing NETs in the stomach, small intestine, pancreas and lungs (specifically atypical carcinoid tumours).

Chronic atrophic gastritis

Some studies show that chronic atrophic gastritis increases the risk of developing NETs in the stomach. Chronic atrophic gastritis is a long-term condition. It makes the lining of the stomach (called the mucosa) inflamed or swollen, which causes it to wear away. Many of the glands that normally make acid, enzymes and mucus are in the lining of the stomach, so these are lost when the lining wears away.

Diabetes

There is some evidence that having diabetes may increase the risk of developing NETs, particularly in the pancreas or stomach. Diabetes (also called diabetes mellitus) is a chronic disease in which the body can’t make insulin or it can’t properly use the insulin it makes. Since the body needs insulin to use and store glucose (a type of sugar) for energy, diabetes leads to high blood sugar levels.

Unknown risk factors

It isn’t known whether or not the following factors are linked with NETs. It may be that researchers can’t show a definite link or that studies have had different results. More research is needed to see if the following are risk factors for NETs: